The proposed research involves studies on glucose 6-phosphate dehydrogenases (G6PD) from three sources: Leuconostoc mesenteroides, developing rabbit erythrocytes, and rat liver. Structural studies on the L. mesenteroides G6PD are designed to elucidate the primary structure of active site peptides. Structural and kinetic studies on G6PD isolated from rabbit erythroblasts are planned in order to establish the molecular basis for the large change in G6PD catalytic activity as the erythroblasts mature from the polychromatic to the orthochromatic stage. Rat liver G6PD is being studied in order to elucidate the molecular basis of the mechanism for overcoming NADPH inhibition which was described by Eggleston and Krebs and which requires oxidized glutathione and an unstable cofactor. The overall goal of this project is to elucidate the molecular bases of the mechanisms whereby various G6PDs are regulated.